It is known that in a normal human patient, there are respiration-induced variations in heart rate. These variations are known as respiratory sinus arrhythmia (RSA). However, in certain patients, the normal respiratory phasic modulation of heart rate may be lacking. For example, in a patient with a conventional pacemaker, e.g., atrial pacing for bradycardia, the respiratory control is missing. There are also cases where improved hemodynamics by respiration-modulated pacing can be beneficial to patients with heart failure. For example, sleep-disordered breathing (periodic or Cheyne-Stokes respiration) is common in patients with advanced stages of heart failure. There are suggestions in the literature that the impaired circulation and heart function may be a causal factor in the development of this breathing disorder, and that improved hemodynamics leads to improved breathing. Accordingly, the advantage of restoring respiration-modulated rate variations may be beneficial to such patients.
Respiratory sinus arrhythmia is also suppressed in patients with severe hypertension due to a low parasympathetic activity. Regardless of the initiating cause of hypertension, the poor RSA and the ensuing variability in ventricular power output may well contribute to the perpetuation of hypertension. Thus, the restoration of RSA may be beneficial to many hypertensive patients. After thoracic surgery, patients are often artificially ventilated and under the influence of sedatives for several days, which condition frequently leads to complications such as atelectasis (fluid accumulation in the lower lung lobes). The complications are due to the positive pressure ventilation which tends to squeeze blood from the lungs and impairs the pulmonary circulation. For such patients, improved respiration-coupled heart rate modulation may aid in normalizing circulation.
It is important to understand the mechanism by which the normal body modulates cardiac rate in accordance with the inspiration/expiration cycle, and the benefit of such modulation. During expiration the relatively high thoracic pressure causes compression of the Vena Cava and a reduction of blood flow toward the right atrium. During inspiration and relative negative pressure the Vena Cava expands and the flow of venous blood to the right atrium increases. This cyclic variation in venous return results in a marked beat-to-beat variation in the stroke volume and power output of the right ventricle. The cyclic variation in heart rate is an adaptation which tends to make the stroke volume and power output per beat more constant. In the elderly and in patients with chronic diseases such as diabetes, heart failure or hypertension, the control of circulation is impaired due to reduced function of the autonomic nervous system. Consequently, the respiration-induced variations in heart rate are much smaller for these patients than for healthy subjects, causing variations in power output and oxygen consumption of the heart. The variable power input into the large arteries may have long-term effects on the vascular walls. This in turn may contribute to the progression of chronic diseases, pulmonary or systemic hypertension and right ventricular failure in particular. Accordingly, the restoration of a respiratory-modulated cardiac rate, by means of an implanted device, would improve this condition for patients with conditions such as hypertension and heart failure, and would provide an additional benefit in conventional pacemaker applications. Further, the advantage may be utilized by an external system for post-surgery, artificially-ventilated patients.
The variation of return of venous blood to the ventricles during respective respiratory phases is an important factor underlying respiratory modulation of heart rate. Inspiration has opposite effects on the pump functions of the right and left ventricles. The decreased intrathoracic pressure during inspiration causes a marked increase in the return of venous blood from the body into the right atrium, and a large end-diastolic volume in the right ventricle. The inspiratory expansion of the lungs leads to an accumulation of blood in the expanding lung vessels and a reduced flow of blood into the left atrium and ventricle, i.e., decreased pre-load. Thus, there is a respiration-induced tidal-type shift of blood volume back and forth between the peripheral and the pulmonary circulation, which causes variations in the pre-load and output of both ventricles.
The enhanced return of blood into the right ventricle during inspiration, and the associated large end-diastolic volume of the RV, inhibits the filling of the left ventricle, because the ventricles share the septum and are mechanically coupled. However, an increased heart rate during inspiration, producing a shorter diastole, reduces somewhat the right ventricular end-diastolic volume, and the inhibition of left ventricle filling. As discussed in greater detail below, an increased heart rate during the inspiration phase makes the power output per beat from the right ventricle more constant. The increased venous return and the increased heart rate during inspiration lead to a rapid filling of the vessels in the expanded lungs. This amplifies the blood pumping action of the lungs. Thus, during inspiration a large amount of blood is pumped into the lung vessels at a low pressure, and a larger amount of blood is stored in the lung vessels. During expiration, the output from the right ventricle is relatively low, and the compression of the lung vessels pumps the stored blood into the left atrium and ventricle. The net effect is a more constant flow of blood into the left atrium during the entire respiratory cycle, part of the required energy being supplied by the mechanics of respiration. The more constant end-diastolic volume of the left ventricle implies a more constant power output per beat, and a more constant oxygen consumption. This is of particular importance to the left ventricle in which myocardial perfusion and oxygen supply is limited to the diastolic periods.
The right ventricle is suitably regarded as a volume pump, providing a volume of blood to the lungs. Its muscular wall is relatively thin and unable to produce high pressures. The power output (pressure.times.flow) is only about 15% of that of the left ventricle. The RV is well-adapted to pump blood through the pulmonary vessels which have a relatively low resistance. Inspiration, as opposed to expiration, is associated with a relatively low intra-thoracic pressure, increased venous return to the right atrium, large end-diastolic volume of the right ventricle, and a large stroke volume. Accordingly, the power output per beat is relatively high during inspiration. The higher heart rate during inspiration yields a shorter diastole, and thus reduces the end-diastolic volume and power output per beat, resulting in a more constant power output.
The situation with respect to the left ventricle is altered by its relative position with respect to the lungs. The expanding lung vessels retain blood during inspiration, and consequently the flow to the left atrium is relatively small. At the same time, the large volume of the right ventricle inhibits left ventricular filling. Both of these effects lead to a small end-diastolic volume of the left ventricle during inspiration. This is, however, counteracted by the increased heart rate which reduces the two above effects. Therefore, the result of a normal RSA is a more constant power output. This is beneficial, since variation of the amount of power stored per beat in the aorta and the pulmonary artery may influence the properties of the arterial walls and play a role in the development or maintenance of hypertension.
RSA is most prominent in supine resting subjects, in particular during deep, non-REM sleep, whereas it is absent during intensive exercise or in general when the heart rate is high. This is related to the balance between sympathetic and parasympathetic influences on the heart. In resting conditions, the parasympathetic influence (via the vagus nerve) dominates and the heart rate is relatively low. During exercise, the sympathetic influence causes a high heart rate and strong contractions.
In view of the above, it is seen that patients in whom the normal RSA is impaired may receive substantial benefit by the restoration of this function so as to provide a relative increase of heart rate during inspiration and relative decrease of heart rate during expiration. A solution to the problem for such patients has not been previously addressed. Reference is made to U.S. Pat. No. 4,791,931, which proposes an artificial baroreflex system comprising a pacemaker with an arterial blood pressure (ABP) sensor. The ABP sensor provides ABP signals which are used by the implantable device to adjust the pacing rate, whereby the pacing rate adjusts to the physiologic baroreflex mechanism. However, this system does not in any way take into account the respiratory phases, and does not provide for rate variations which alter the power output of the ventricles. Respiration signals have been used in rate-adaptive pacemakers, for the limited purpose of increasing heart rate during exercise. However, such applications respond only slowly to respiration frequency, and do not provide in any sense the type of respiration modulation required to restore the RSA function. Accordingly, for patients with impaired RSA function there remains a need for restoration of some measure of the RSA function.